The aim of this study was to evaluate the effect of 21-aminosteroid
lipid peroxidation inhibitor,
U74006F, on ischaemic brain tissue damage using the rat
middle cerebral artery occlusion model. Under anaesthesia, the left middle cerebral artery was exposed without cutting the dura mater via a subtemporal
craniotomy, under an operating microscope. Photo-illumination (wave length; 540 nm) was applied to the middle cerebral artery and then
rose bengal (20 mg/kg) was administered intravenously. The middle cerebral artery was completely occluded by
thrombus about 6 min after the administration of
rose bengal.
U74006F (1.0 mg/kg) was then injected intravenously just after the cessation of illumination. Twenty four hours after the operation, the extent of ischaemic damage was measured by magnetic resonance imaging technique. After measuring the extent of ischaemic damage, the brain was immediately removed from animals treated with or without
U74006F for determination of lipid peroxidation, and the generation of free
arachidonic acid in the brain.
U74006F significantly (P < 0.01) reduced the size of ischaemic damage. Twenty-four hours after the operation, lipid peroxidation and the concentration of free
arachidonic acid in the left hemisphere (
infarction side) were significantly (P < 0.05) higher than in the right hemisphere.
U74006F significantly (P < 0.05) decreased the content of lipid peroxidation products and free
arachidonic acid. There was a significant (P < 0.05) correlation between the extent of ischaemic damage and the concentration of lipid peroxidation products in the left hemisphere 24 h after the operation. In conclusion,
U74006F might reduce the extent of ischaemic damage by inhibiting lipid peroxidation in the brain, thus minimizing oxidative damage to neural tissues.